Project Summary/Abstract Bronchopulmonary dysplasia (BPD), the major chronic lung disease of infancy, remains the most common severe complication of extremely preterm birth, affecting approximately half of infants born at ?28-weeks gestation. BPD persists as a leading cause of mortality and respiratory impairments in preterm infants. Lung dysfunction, airway obstruction, and pulmonary hypertension often persist into adulthood. Associated neurodevelopmental impairments include global cognitive delays, cerebral palsy, language and learning delays, and behavioral problems. Unlike mortality and other major preterm birth-associated morbidities, BPD rates have not declined over the past decade. The goal of treatment is to reduce BPD severity, which is commonly measured at 36-weeks postmenstrual age (PMA) (birth gestation + postnatal age), the age at which BPD severity predicts persistent pulmonary disease and long-term neurodevelopmental delay. With the exception of supportive care, safe proven treatments for BPD are extremely limited, leading many clinicians to prescribe unproven, off-label treatments including diuretics and inhaled corticosteroids (ICS) based on the theory that a reduction of lung inflammation and fluid retention may be therapeutic. These treatments are controversial given limited evidence of their benefit and the risk of harmful side effects. Likely due to the absence of clear evidence, there is marked practice variation between hospitals in the use of diuretics and ICS to treat BPD. Our objective in this investigation is to utilize ?real-world? patient data to determine whether diuretic and inhaled corticosteroid treatments for evolving and established BPD reduce mortality and severity of BPD in preterm infants at 36-weeks PMA, as compared to no treatment. In Aim 1, we will determine if diuretic and inhaled corticosteroid treatments of infants with evolving BPD (at postnatal day 10), compared to no treatment, are associated with improvement in mortality and BPD severity at 36-weeks PMA. We will include diuretic and ICS treatments prescribed from postnatal days 10-27, inclusive. In Aim 2, we will determine if diuretic and inhaled corticosteroid treatments of infants with established BPD (at postnatal day 28), compared to no treatment, are associated with improvement in mortality and BPD severity at 36-weeks PMA. We will include diuretic and ICS treatments prescribed from 28 postnatal days until 36-weeks PMA. Data will be drawn from the Pediatric Health Information System (PHIS), an administrative database inclusive of most large, children's hospitals within the United States. PHIS contains a daily medication record and a daily respiratory support record for each patient. To reduce confounding and better estimate the effects of diuretic and ICS treatment for evolving and established BPD on mortality and BPD severity, we will employ causal inference methodology including a new-user design and marginal structural modeling using inverse probability of treatment weighting (IPTW). The findings of the proposed investigation will inform clinical treatment decisions for preterm infants with evolving and established BPD and aid the design of future prospective investigations.